Szmuszkovicz U.S. Pat. No. 3,468,881 discloses some allylic amines, having anti-depressive action of the formula ##STR2## wherein the group ##STR3## is selected from the group consisting of pyrrolidino, piperidino, morpholino, 4-methylpiperazino and hexahydro-1H-azepin-1-yl(hexamethyleneimino), and wherein R', R" and R'" are hydrogen or C.sub.1 to C.sub.4 -alkyloxy. However, such compounds are less potent as analgesic and antidepressant compounds.
Szmuszkovicz U.S. Pat. No. 3,506,670 discloses some 1,3-amino-alcohols of the formula ##STR4## wherein --N Z is a heterocyclic amino radical containing from five to ten nuclear atoms, inclusive, e.g., pyrrolidino, 2-methylpyrrolidino, 2-ethylpyrrolidino, 2,2-dimethylpyrrolidino, 3,4-dimethylpyrrolidino, 2-isopropylpyrrolidino, 2-sec.-butylpyrrolidino, and like alkylpyrrolidino groups, morpholino, 2-ethylmorpholino, 2-ethyl-5-methylmorpholino, 3,3-dimethylmorpholino, thiamorpholino, 3-methylthiamorpholino, 2,3,6-trimethylthiamorpholino, 4-methylpiperazino, 4-butylpiperazino, piperidino, 2-methylpiperidino, 3-methylpiperidino, 4-methylpiperidino, 4-propylpiperidino, 2-propylpiperidino, 4-isopropylpiperidino, and like alkylpiperidino groups, hexamethyleneimino, 2-methylhexamethyleneimino, 3,6-dimethylhexamethyleneimino, homomorpholino, 1,2,3,4-tetrahydroquinolyl, heptamethyleneimino, octamethyleneimino, 3-azabicyclo[3.2.2]nonan-3-yl, 2-azabicyclo[2.2.2]octan-2-yl, and the like, and R', R", R'", R, R.sup.2 and R.sup.3 are defined variously as hydrogen, halogen, lower alkyl, lower alkoxy or trifluoromethyl, which are disclosed as being useful as oral and parenteral diuretics in mammals. But such patent does not teach the compounds claimed herein or the use as analgesics, claimed herein.
Szmuszkovicz U.S. Pat. No. 3,705,176 discloses some 1,3-aminoalcohol compounds of the formula ##STR5## as oral antidiabetic agents. This patent defines ##STR6## as a heterocyclic amino radical similar to the definitions above for defining the ##STR7## in the U.S. Pat. No. 3,506,670 patent, but does not include any azetidine compounds therein.
Pain is a major health problem since it is a concomitant of myriads of illnesses. It is especially troublesome in chronic illness because: (1) many strong analgesics lose their effectiveness when given for long periods of time, and (2) continued suffering plus the resultant restrictions on activity often lead to a state of depression, which further inhibits activity and the enjoyment of life. There is a need for a good analgesic which does not cause tolerance during chronic use. Associated antidepressant activity might also prevent or alleviate the depressive element in chronic illness.
The available strong analgesics, narcotics, are also limited by government restrictions, because of the potential for abuse, and by their side effects, which can range from nuisance to life-threatening. Among these are respiratory depression, physical dependence, hallucinations, constipation, urinary retention and precipitation of opiate withdrawal. These qualities, taken with the decreasing effectiveness of chronically administered opiates, mean that there is inadequate treatment for patients with substantial chronic pain.
A number of patents have issued recently describing various N-(2-aminocycloaliphatic)benzeneacetamide derivative compounds (e.g. U.S. Pat. No. 4,145,435) and N-(2-aminocycloaliphatic)benzamide derivative compounds (e.g., U.S. Pat. No. 4,098,904) as analgesic compounds. These above patents have included within their description definitions of the 2-amino groups thereof as including azetidinyl rings as the amino group. However, those compounds are 2-amino-cycloaliphaticamide compounds (bearing 2 nitrogens on positions 1 and 2 of the cycloaliphatic ring) and function somewhat differently than the new compounds described and claimed herein.